Coronary atherosclerosis is a major cause of death in women in the USA. Although coronary artery bypass surgery decreases symptomatic and clinical evidence of ischemia, it does not alter the underlying process. Patients may present several years later with recurrent symptoms that may be a result of occlusion of saphenous vein grafts, development of atherosclerotic disease in the vein gratfs, or progression of underlying disease. Any intervention that can reduce the rate of progression of coronary atherosclerosis following bypass surgery would provide significant benefit for women following bypass surgery and possbily for other women with atherosclerotic disease. Observational studies suggest that postmenopausal hormone replacement therapy reduces cardiac morbidity. However, the benefit for hormone replacement therapy in women with established coronary disease has not been demonstrated. This randomized, double-blind controlled trial tests the hypothesis that postmenopausal hormone replacement therapy in women following coronary bypass surgery will reduce the occurrence of graft occulsion and delay the development of graft atherosclerosis. Women will be randomized to estradiol and medroxyprogesterone or placebo within 8 weeks of bypass surgery. Graft occlusion and development of vein graft atherosclerosis will be measured by comparing quantitative coronary angiographic and intravascular ultrasonographic assessment of disease severity and extent performed at 6 months and 3.5 years after randomization. The primary outcome variable will be progression of graft and native vessel disease over the 3.5 years of therapy. Secondary outcome variables will be the occurrence of graft occulsion at 6 months, and the change in severity of atherosclerosis in the saphenous vein grafts over 3 years as assessed by IVUS. The pathophysiologic mechanisms of interest in this proposal are the effects of hormone replacement on platelet activation, fibrinogen binding to platelets, vascular reactivity, coagulation and fibrinolytic factors. The trial is in the recruitment phase.